OBJECTIVES: Patients receiving mechanical ventilation are at an increased risk of pneumonia, which can prolong hospital stays and increase costs. There are limited national data on the costs of ventilator-associated pneumonia (VAP) due to Staphylococcus aureus, a common hospital-acquired pathogen. METHODS: This retrospective cohort study used data from the 2004 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS). Ventilator-dependent patients with S. aureus pneumonia were identified based on ICD-9-CM diagnosis and procedure codes and compared to ventilator-dependent patients without a diagnosis of pneumonia. Excess length of stay (LOS) and costs were estimated. Multivariate models were used to adjust costs for potential confounding factors, including age, gender, mortality, hospital region, and comorbidity. RESULTS: We identified 198,269 hospitalized patients who required use of a ventilator, of whom 9,592 (4.8%) were identified as having S. aureus pneumonia. Patients with VAP due to S. aureus were older (mean age 62 years vs. 49 years for the comparison group) and were more likely to have congestive heart failure, chronic pulmonary disease, diabetes and bacteremia/septicemia. Relative to the comparison group, patients with VAP due to S. aureus had significantly (P<.001) longer mean length of stay (25.6 vs. 14.5 days) and substantially higher average costs per stay ($72,820 vs. $40,171). After controlling for potentially confounding factors, the excess costs associated with VAP due to S. aureus were estimated to be approximately $14,000. CONCLUSION: Our findings suggest that the economic burden of ventilator-associated pneumonia (VAP) due to Staphylococcus aureus among hospitalized patients is substantial. Further research is needed to assess the value of large hospital discharge databases for documenting and distinguishing the costs of specific bacterial pathogens.